Metribuzin is produced commercially in large quantities and extensively used as a herbicide for undesired vegetation associated with soybeans. Preventing or minimizing loss of a portion of such a valuable crop, with over 60 million metric tons annual production [Sci. Amer., 235, 88 (1976)], by inhibiting the growth or killing undesired competing vegetation, is a significant approach to improving agricultural efficiency. More than 25 million acres under soybean cultivation are estimated to have utilized a weed control program incorporating metribuzin in 1981.
U.S. Pat. No. 3,905,973 discloses the methylation of butylthion to yield metribuzin using methyl chloride as the methylating agent in the presence of iodide ion. The required use of iodide compounds does not enable the greatest economy, and a mixture of methyl isomers is produced which reduces the yield of active product.
U.S. Pat. No. 3,897,429 discloses the methylation of butylthion using methyl bromide in water or in aqueous alcohol, ketone, or amide solutions at a single temperature in the range -15.degree. C. to +30.degree. C. in the presence of alkali metal hydroxide utilizing a single contacting of the reagents to make metribuzin. Mixtures of water and organic solvents are only proposed to maintain a liquid phase if a reaction temperature below 0.degree. C. is used. The patent further discloses the regeneration of methyl bromide by reaction of used process supernatant with methyl alcohol and sulfuric acid in a 15-25% excess after first removing water by distillation to concentrate the sodium bromide solution produced by the reaction of butylthion with methyl bromide in the presence of sodium hydroxide. The regenerated methyl bromide is then reused directly in a subsequent methylation reaction. It has now been discovered that a greater yield and purity of metribuzin can be achieved using a temperature profile during the reaction of butylthion and methyl bromide, and that even greater economy can be achieved by regenerating methyl bromide with a greater excess of sulfuric acid.
U.S. Pat. No. 4,035,364 discloses modifications in the basic process of methylation of butylthion claimed in the '429 patent described above. In particular, the patent discloses reaction in aqueous media in the substantial absence of air, the use of alkyl aryl polyglycol ether emulsifier, and the possible one-time partial reuse of methylation process reagents. The procedure disclosed for regeneration of methyl bromide involves concentrating all solutions to dryness and subsequently reacting solid sodium bromide with methanol and sulfuric acid. Partial, one-time reuse of methylation process reagents does not achieve maximum economy, or produce a sufficiently high concentration of sodium bromide to reduce evaporative energy requirements during methyl bromide regeneration. In addition, evaporation of the reaction supernatant to dryness prior to methyl bromide regeneration is wasteful of energy.
U.S. Pat. No. 3,890,317 discloses the methylation of butylthion using process equipment including a filter or a centrifuge to enable continuous removal of metribuzin from the reaction mixture using water as the preferred solvent. The process disclosed can operate in either a batch or continuous mode.